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基于 UPLC-Q-TOF/MS 的“成分-靶点-通路”网络快速筛选旱莲草治疗阿尔茨海默病的活性成分及作用机制

Rapid screening of active ingredients and action mechanisms of Ecliptae Herba for treating Alzheimer's disease by UPLC-Q-TOF/MS and "component-target-pathway" network.

机构信息

School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Department of Pharmacy, Tianjin First Central Hospital, Tianjin 300192, China.

出版信息

Fitoterapia. 2023 Sep;169:105613. doi: 10.1016/j.fitote.2023.105613. Epub 2023 Jul 15.

DOI:10.1016/j.fitote.2023.105613
PMID:37454776
Abstract

Alzheimer's disease (AD) is a common neurodegenerative disease. The drugs widely used in clinic are mainly single-target drugs for symptomatic treatment, which can only alleviate symptoms to a certain extent. Ecliptae Herba (EH) is considered a potential therapeutic drug for AD due to its neuroprotective effects. Although EH has a clear anti-AD effect, the material basis and mechanism remain unclear. Therefore, we adopted an efficient analytical technique, namely ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), combined with "component-target-pathway" network to explore the active components and potential mechanisms of EH in treating AD. Due to the high sensitivity of UPLC-Q-TOF/MS, a total of 50 components were identified in EH. Among them, 20 and 12 compounds were found in plasma and brain samples, respectively. The network pharmacology analysis revealed that apigenin, luteolin, ecliptasaponin A, chlorogenic acid, wedelolactone, and quercetin were the active components, which could affect the serotonergic synapse, calcium and cAMP signaling pathways by regulating related targets such as EGFR, PRKCA, BRAF and ERBB2. This study clarified that EH can exert anti-AD effect through multi-component, multi-target and multi-pathway characteristics. Furthermore, it offers a good foundation for further in-depth research on the anti-AD effects of EH, and provides a valuable approach for the rapid screening of active components and potential mechanisms of other medicinal plants, potentially bringing changes to the discovery and development of novel therapeutics for neurodegenerative disorders.

摘要

阿尔茨海默病(AD)是一种常见的神经退行性疾病。临床上广泛使用的药物主要是针对症状的单靶点药物,只能在一定程度上缓解症状。由于具有神经保护作用,墨旱莲(EH)被认为是一种有潜力的 AD 治疗药物。尽管 EH 具有明确的抗 AD 作用,但物质基础和机制仍不清楚。因此,我们采用了一种高效的分析技术,即超高效液相色谱四极杆飞行时间质谱联用(UPLC-Q-TOF/MS),结合“成分-靶点-通路”网络,探讨 EH 治疗 AD 的活性成分和潜在机制。由于 UPLC-Q-TOF/MS 的高灵敏度,共鉴定出 EH 中的 50 种成分。其中,在血浆和脑组织样本中分别发现了 20 种和 12 种化合物。网络药理学分析表明,芹菜素、木犀草素、旱莲苷 A、绿原酸、异泽兰黄素和槲皮素是活性成分,可通过调节 EGFR、PRKCA、BRAF 和 ERBB2 等相关靶点,影响 5-羟色胺能突触、钙和 cAMP 信号通路。本研究阐明了 EH 通过多成分、多靶点和多通路的特点发挥抗 AD 作用。此外,为进一步深入研究 EH 的抗 AD 作用提供了良好的基础,为快速筛选其他药用植物的活性成分和潜在机制提供了有价值的方法,可能为神经退行性疾病新疗法的发现和开发带来变革。

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